Mechanism of Action of Bacterial Endotoxin

Abstract

THE amount of endotoxin required to produce fatal traumatic shock by the intracerebral route is roughly one-twentieth of that required by the intravenous route¹. The smaller dose is harmless when given intravenously. Shock following the injection of endotoxin into the brain is therefore the result of an action on the peripheral vessels from a distance—through the sympathetic nervous system. Since the site of the critical lesion produced by sympathetic nerve hyperactivity is in the splanchnic viscera, blockade of the coeliac plexus was used in an effort to prevent the critical lesion. In a previous communication we reported that coeliac blockade by ganglionectomy or by a long-lasting regional anaesthetic prevents death in dogs and rabbits from shock produced by endotoxin given intravenously or intracerebrally¹. Some 65 per cent of dogs and rabbits survived a degree of shock that would have produced a mortality exceeding 85 per cent in animals without blockade. Therefore, while endotoxin appears to be capable of acting directly on certain tissues (for example, granulocytes, platelets), the lethal effects of endotoxin appear to be mediated by the catecholamines released in the splanchnic tissues.